MINISTRY OF
EDUCATION AND TRAINING
VIETNAM ACADEMY OF
SCIENCE AND TECHNOLOGY
GRADATE UNIVERSIY OF SCIENCE AND TECHNOLOGY

LE THE TAM
STUDY ON THE FABRICATION OF MAGNETIC FLUIDS BASED ON
SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES (SPIONs)
APPLIED TO MAGENTIC RESONANCE IMAGING (MRI)
APPLICATION
Major: Inorganic chemistry
Code: 9.44.01.13
SUMMARY OF CHEMISTRY DOCTORAL THESIS
Ha Noi - 2019
This thesis was done at:
Laboratory of Biomedical Nanomaterials, Institute of Materials and Sciene,
Vietnam Academy of Science and Technology.
Laboratory of Electronic-Electrical Engineering, Institute for tropical
technology, Vietnam Academy of Science and Technology.
Centre for Pratices and Experimences, Vinh University.
Supervisor: Prof., Dr. Tran Dai Lam
Assoc.Prof., Dr. Nguyen Hoa Du
Reviewer 1: .....................................................
Reviewer 2: .....................................................
Reviewer 3: .....................................................
The dissertation will be defended at Graduate University of Science and Technology, 18
Hoang Quoc Viet street, Hanoi.
Time: .............,.............., 2019
This thesis could be found at National Library of Vietnam, Library of Graduate
University of Science and Technology, Library of Chemistry, Library of Vietnam
Academy of Science and Technology.
INTRODUCTION
Recent applications of magnetic nanoparticles in biomedical applications, especially in
imaging diagnostics using MRI Magnetic Resonance Imaging engineering have attracted the
attention of scientists around the world. Currently in imaging diagnostics using MRI magnetic
resonance imaging, Tl contrast agents have become a traditional commodity, which is a
complex of paramagnetic ions with a large torque value like Gd3+ (7 unpaired electrons).
These Gd3+ ions are combined with molecules such as DTPA (diethylentriamine penta acetic
acid) and create Gd-DTPA chelate round complex structures. During the recovery process,
the interaction between the magnetic moment of the proton and the magnetic moment of the
paramagnetic ions causes the T1 time to be reduced, so the recovery rate R1 increases. The
concentration of agents is different in each cell tissue region, thus providing an effective
contrasting on MRI images. For nearly 10 years now, along with the development of
nanotechnology iron oxide (IO) nanoparticle having been strongly researched and actual
many commercial products that increase MRI contrast levels using this iron oxide material,
proving that iron oxides-MRI can give better quality of contrast level than Gd-DTPA because
iron oxide particles have a higher magnetic induction coefficient. IO-MRI substances can
reduce both T1 and T2, increasing MRI recovery rates in both Tl and T2 MRI modes. The
important requirements for MRI contrast increasing products are that magnetic nanoparticles
must have a relatively uniform particle distribution and magnetic saturation enough large, and
the coating materials must have good biological compatibility. While some commercial
products in the world, such as Resovist, use dextran as a coating material, with a 65 nm core
particle created from saturation of about 65 emu/g. Products with particle sizes in the 20-
40nm region such as AMI-227: Sinerem/Combidex are suitable for lymph and bone. In the
last 10 years, people have been studying to create superparamagnetic nanoparticles with a
particle size smaller than 20 nm (also known as microscopic if the particle size is D<10 nm)
and especially iron oxide particles, marked with magnetic markers is intended for MRI
targeted imaging.
In Vietnam, up to now the fabrication of nanoparticles in general and magnetic
nanoparticles in particular has been focused to research in accordance with two aspects: basic
research and application-orientation research. The profound research results are published
mainly from large research institutions such as: Hanoi National University, Hanoi University
of Science and Technology and Vietnam Academy of Science and Technology. The synthesis
of magnetic nanomaterials is mostly carried out in water and by synthetic methods such as
co-precipitation methods, hydrothermal methods, microwave methods and ultrasonic
electrochemical synthesis methods. Due to the synthesis in the water environment, the
fabricated magnetic nanoparticles have not high quality, the particles are uneven in size and
heterogeneous in shape and therefore they are restricted for use in vivo printing applications
in biomedicine such as used as a contrast drug in imaging diagnosis by MRI magnetic
resonance imaging, magnetic induction heating, etc. in addition, the such unevenness even
affects the research results of their magnetic properties. Therefore, up to now, the selection
of conditions in the fabrication of Fe3O4 nano magnetic fluid to produce particles with small
particle size, uniform distribution, homogeneous shape and high durability, high magnetism
and high biocompatibility, thus making it possible to apply as contrast medicine in imaging
diagnostics using MRI magnetic resonance imaging, creating optimal values of impulses TR,
TE when taking with T1, T2 mode, and determining recovery coefficient r1, r2 to assess the
quality of magnetic fluids as contrast medicine in imaging diagnosis by MRI magnetic
resonance imaging is still asking for continuing and systematic research.
Derived from the research on nanomaterials in the world as well as in Vietnam, based
on the research and Doctor training potential of the Institute of Science and Technology,
Vietnam Academy of Science and Technology, under the guidance of a group of experienced
scientists, we select the topic "Study on the fabrication of magnetic fluids based on
superparamagnetic iron oxide nanoparticles (SPIONs) applied to magentic resonance
imaging (MRI) application" to make this thesis content.
Research object of the thesis:
Magnetic fluid system based on superparamagnetic iron oxide.
Research targets of the thesis:
The goad of the thesis is to build the manufacture process of nano-sized magnetic fluids
based on iron oxide (uniform particle size and high magnetic saturation) with stable
technology; Characteristic research of magnetic properties of magnetic nanoparticles;
assessment of toxicity and test of effects on cells, aiming to make contrast medicine in
imaging diagnosis by magnetic resonance imaging (MRI), application on accurately
identifying cancer.
Scientific and practical meaning of the thesis:
The implementation organization of the topic itself has important implications for
developing a multi-disciplinary science and technology direction as Nanotechnology for
Medicine. There will be academic exchange, mutual learning between research groups in the
industries deem as independent. Scientifically, the magnetization of magnetic particle systems
for biomedical applications is strongly influenced by many factors, but the mechanism of
these effects is still a problem that has not been studied fundamentally.
For the application of cancer diagnosis and treatment, nanotechnology in general is
creating a great expectation that is able to contribute to solve the problem of early disease
diagnosis and drugs to target or intervention areas localized at the destination. The subject has
a goal of using magnetic fluid improving the contrast of nuclear magnetic resonance imaging
(MRI), which can contribute to the analysis of early-stage cancer tissue.
Research methodology:
The thesis is conducted by experimental method combined with numerical calculation
techniques. The research sample is fabricated by hydrothermal and thermal decomposition
methods. Study the structure of the sample by X-ray diffraction techniques (XRD), electron
microscopy (FESEM, TEM and HRTEM). The magnetic properties of the materials are
surveyed by magnetic measurements on the vibrating sample magnetometer (VSM) system.
Using Fourrier Transformation InfraRed (FTIR), Thermal gravimetric analysis (TGA) to
evaluate the presence of functional groups on the particle surface and the mass reduction of
polymer-coated magnetic particle layer. Dynamic Light Scattering (DLS) technique
determines the hydrodynamic size and durability of magnetic fluids. Experimental assessment
of toxicity through in-vitro test. MRI imaging method T1, T2 for studies of contrast
enhancement of material samples for manufacturing (on 1.5T MRI scanner, SIEMENS
MAGNETOM, Germany).
Research contents of the thesis:
1. Successful summary of Fe3O4 magnetic nanoparticles with uniform particle size and
high saturation magnetization by hydrothermal and thermal decomposition methods.
2. Successfully fabrication of high-strength magnetic fluids on Fe3O4 particles
synthesized by the above two methods.
3. Research on the toxicity and durability of magnetic fluids.
4. Study the applicability of image contrast enhancer in MRI magnetic resonance
imaging.
The layout of the thesis:
The thesis has 137 pages (not including references, appendices), including the
introduction, 5 chapters of content and conclusions.
The main results of the thesis are published in 09 published projects, including 01 article
published under SCI list, 01 article sent from SCI list submitted and reviewing, 05 articles on
National magazine, 01 article published in the Proceedings of the National Science
Conference, and registered 01 intellectual property (SC) has been published in the volume A
Industrial Ownership Gazette.
Main results of the thesis:
The influence and optimization of technological conditions on the structure and
magnetic properties of chitosan-coated Fe3O4 nanoparticles (CS) were investigated using
hydrothermal method.
Successfully fabricated magnetic fluids based on Fe3O4 particles by thermal
decomposition method by phase transformation and coating by polymer PMAO.
Fe3O4@PMAO liquid samples are highly durable in different conditions, single-dispersed,
uniform particles.
Evaluation of the toxicity of magnetic fluids on typical samples with different cell lines,